tbuckley/cabot-search huggingface dataset:
Smoking Cessation and Pancreatic Cancer Risk in Individuals With Prediabetes and Diabetes: A Nationwide Cohort Study
Authors: Joo-Hyun Park, Jung Yong Hong, Jay J. Shen, Kyungdo Han, Young Suk Park, Joon Oh Park
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Individuals with diabetes and prediabetes are at increased risk of pancreatic cancer. However, little is known about the effects of smoking or smoking cessation on pancreatic cancer risk in individuals with diabetes and prediabetes. We investigated the association between smoking status (particularly smoking cessation) and pancreatic cancer risk according to glycemic status. Patients and Methods: This nationwide cohort study included 9,520,629 adults without cancer who underwent the Korean National Health Screening in 2009 and were followed until 2018. Hazard ratios and 95% confidence intervals for pancreatic cancer were estimated after adjusting for potential confounders. Results: During the 78.4 million person-years of follow-up, 15,245 patients were newly diagnosed with pancreatic cancer. Among individuals with diabetes and prediabetes, current smoking synergistically increased pancreatic cancer risk (all P &lt;.01). However, quitters with diabetes and prediabetes had a pancreatic cancer risk comparable to that of never-smokers (all P &gt;.05). For pancreatic cancer in current smokers, quitters, and never-smokers, respectively, the hazard ratios were 1.48 (95% CI, 1.40–1.58), 1.11 (95% CI, 1.03–1.19), and 1.00 (reference) among individuals with normoglycemia; 1.83 (95% CI, 1.70–1.97), 1.28 (95% CI, 1.18–1.39), and 1.20 (95% CI, 1.14–1.26) among individuals with prediabetes; and 2.72 (95% CI, 2.52–2.94), 1.78 (95% CI, 1.63–1.95), and 1.63 (95% CI, 1.54–1.72) among individuals with diabetes. There were no differences in risk between quitters with a &lt;20 pack-year smoking history and never-smokers in all glycemic status groups. Conclusions: Pancreatic cancer risk synergistically increased in current smokers with diabetes and prediabetes. However, smoking cessation reduced the synergistically increased risk of pancreatic cancer to the level of never-smokers, especially when smoking history was &lt;20 pack-years. More individualized and intensive cancer prevention education should be underscored for individuals at an increased risk of pancreatic cancer beyond the one-size-fits-all approach.
Referral, Uptake, and Outcome of Genetic Counseling and Testing in Patients With Early-Onset Colorectal Cancer
Authors: Hareem Syed, Joshua Sommovilla, Carol A. Burke, Sarah McGee, Carole Macaron, Brandie Heald, Ruishen Lyu, Stephanie L. Schmit, Kanika Nair, Suneel Kamath, Smitha Krishnamurthi, Alok A. Khorana, David Liska
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: The incidence of early-onset colorectal cancer (EOCRC) is rapidly increasing. Pathogenic germline variants (PGVs) are detected in 16% to 20% of patients who have EOCRC, highlighting a need for genetic counseling (GC) and multigene panel testing in these patients. We aimed to determine the rate of referral to GC and uptake and outcomes of germline testing in patients with EOCRC. Methods: We conducted a retrospective cohort study of patients aged &lt;50 years diagnosed with colorectal cancer (CRC) from 2010 to 2019 at Cleveland Clinic. Demographic data were extracted, including age, sex, self-reported race, and family history of CRC. The proportions of patients with GC referral and completion of GC and genetic testing were investigated, and genetic testing results were analyzed. Multivariable logistic regression analysis was conducted to identify factors independently associated with GC referral and uptake. Results: A total of 791 patients with EOCRC (57% male and 43% female) were included; 62% were referred for GC, and of those who were referred, 79% completed a GC appointment and 77% underwent genetic testing. Of those who underwent testing, 21% had a PGV detected; 82% were in known CRC-associated genes, with those associated with Lynch syndrome and familial adenomatous polyposis the most common, and 11% were in other actionable genes. Referral to GC was positively associated with family history of CRC (odds ratio [OR], 2.11; 95% CI, 1.51–2.96) and more recent year of diagnosis (2010–2013 vs 2017–2019; OR, 5.36; 95% CI, 3.59–8.01) but negatively associated with older age at diagnosis (OR, 0.89; 95% CI, 0.86–0.92). Conclusions: Referral to GC for patients with EOCRC is increasing over time; however, even in recent years, almost 25% of patients were not referred for GC. We found that 1 in 5 patients with EOCRC carry actionable PGVs, highlighting the need for health systems to implement care pathways to optimize GC referral and testing in all patients with EOCRC.
Should We Use COMM (Current Opioid Misuse Measure) to Screen for Opioid Abuse in Patients With Cancer Pain?
Authors: Natalie Moryl, Tito R. Mendoza, Susan D. Horn, Jelyn C. Eustaquio, Charles S. Cleeland, Charles Inturrisi
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Growing concerns about opioid use disorder (OUD) and the resulting decrease in opioid availability for patients with cancer pain highlight the need for reliable screening tools to identify the subset of patients at increased risk for aberrant opioid use. Our study examines the utility of Current Opioid Misuse Measure (COMM) recommended by the NCCN Clinical Practice Guidelines in Oncology for Adult Cancer Pain. Patients and Methods: We analyzed prospectively collected patient-reported outcomes of 444 consecutive patients with cancer seen in pain clinics of a cancer center at 2 time points within 100 days. The relationship of COMM to other OUD screening tools, pain, opioid doses, patient demographics, and mortality was examined using univariate and multivariable logistic regression. We also examined individual items of COMM for face validity. Results: Among 444 patients who completed pain surveys at 2 time points, 157 (35.4%) did not complete COMM surveys. Using a COMM cutoff of ≥13, a total of 84 patients (29.3%; 84/287) scored positive for aberrant drug use. As patients remained on opioids for 49 to 100 days, the likelihood of improving COMM score (turning from positive to negative) was 6.1 times greater than the reverse. The number of patients with COMM ≥13 was 3.8 times higher than the number of patients with CPT diagnostic codes for OUD, 5.3 times higher than those with a positive urine drug screening, and 21 times higher than those with a positive CAGE (Cut Down, Annoyed, Guilty, Eye-Opener Questionnaire) score. COMM ≥13 was not associated with pain relief response (worst pain intensity score ≥2 points on the Brief Pain Inventory), opioid doses, gender, or age. Contrary to the intended use of COMM to identify aberrant opioid use, COMM ≥13 predicted mortality: patients with COMM ≥13 were 1.9 times more likely to die within 12 months. Conclusions: Our study found that using COMM in a cancer population may significantly overestimate the risk of opioid misuse. Using COMM without modifications can create an additional barrier to cancer pain management, such as limiting appropriate opioid use.
Acute and Chronic Complications After Treatment of Locoregional Anal Cancer: Prevention and Management Strategies
Authors: Leah Katz, David P. Horowitz, Lisa A. Kachnic
Journal: Journal of the National Comprehensive Cancer Network (2023)

Definitive chemoradiotherapy (CRT) for anal cancer spares patients the morbidity of a colostomy surgery and optimizes cancer outcomes. CRT, however, has introduced a unique acute and chronic toxicity profile, which has greatly improved over the years with the introduction of advanced radiotherapy techniques. This article provides the multidisciplinary care team with practical tools to mitigate and manage acute and chronic complications from definitive treatment of anal cancer.
Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology
Authors: Chrysalyne D. Schmults, Rachel Blitzblau, Sumaira Z. Aasi, Murad Alam, Arya Amini, Kristin Bibee, Jeremy Bordeaux, Pei-Ling Chen, Carlo M. Contreras, Dominick DiMaio, Jessica M. Donigan, Jeffrey M. Farma, Karthik Ghosh, Kelly Harms, Alan L. Ho, John Nicholas Lukens, Lawrence Mark, Theresa Medina, Kishwer S. Nehal, Paul Nghiem, Kelly Olino, Soo Park, Tejesh Patel, Igor Puzanov, Jason Rich, Aleksandar Sekulic, Ashok R. Shaha, Divya Srivastava, Valencia Thomas, Courtney Tomblinson, Puja Venkat, Yaohui Gloria Xu, Siegrid Yu, Mehran Yusuf, Beth McCullough, Sara Espinosa
Journal: Journal of the National Comprehensive Cancer Network (2023)

Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise. Exposure to radiation, from either sunlight or previous medical therapy, is a key player in BCC development. BCC is not as aggressive as other skin cancers because it is less likely to metastasize. However, surgery and radiation are prevalent treatment options, therefore disfigurement and limitation of function are significant considerations. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline an updated risk stratification and treatment options available for BCC.
NCCN Guidelines® Insights: B-Cell Lymphomas, Version 6.2023
Authors: Andrew D. Zelenetz, Leo I. Gordon, Jeremy S. Abramson, Ranjana H. Advani, Babis Andreadis, Nancy L. Bartlett, L. Elizabeth Budde, Paolo F. Caimi, Julie E. Chang, Beth Christian, Sven DeVos, Bhagirathbhai Dholaria, Luis E. Fayad, Thomas M. Habermann, Muhammad Saad Hamid, Francisco Hernandez-Ilizaliturri, Boyu Hu, Mark S. Kaminski, Yasmin Karimi, Christopher R. Kelsey, Rebecca King, Susan Krivacic, Ann S. LaCasce, Megan Lim, Marcus Messmer, Mayur Narkhede, Rachel Rabinovitch, Praveen Ramakrishnan, Erin Reid, Kenneth B. Roberts, Hayder Saeed, Stephen D. Smith, Jakub Svoboda, Lode J. Swinnen, Joseph Tuscano, Julie M. Vose, Mary A. Dwyer, Hema Sundar
Journal: Journal of the National Comprehensive Cancer Network (2023)

Novel targeted therapies (small molecule inhibitors, antibody–drug conjugates, and CD19-directed therapies) have changed the treatment landscape of relapsed/refractory B-cell lymphomas. Bruton’s tyrosine kinase (BTK) inhibitors continue to evolve in the management of mantle cell lymphoma (MCL), in both the relapsed/refractory and the frontline setting. Anti-CD19 CAR T-cell therapies are now effective and approved treatment options for relapsed/refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and MCL. Bispecific T-cell engagers represent a novel immunotherapeutic approach for relapsed FL and DLBCL after multiple lines of therapies, including prior CAR T-cell therapy. These NCCN Guideline Insights highlight the significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, DLBCL, and MCL.
Associations Between Surrogates’ Decisional Regret Trajectories and Bereavement Outcomes
Authors: Fur-Hsing Wen, Chia-Hsun Hsieh, Wen-Chi Shen, Ming-Mo Hou, Po-Jung Su, Wen-Chi Chou, Jen-Shi Chen, Wen-Cheng Chang, Siew Tzuh Tang
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Family surrogates experience heterogeneous decisional regret and negative long-lasting postdecision impacts. Cross-sectional findings on the associations between decisional regret and surrogates’ bereavement outcomes are conflicting and cannot illustrate the directional and dynamic evolution of these associations. In this study, we sought to longitudinally examine the associations between 4 previously identified decisional-regret trajectories and bereavement outcomes among family surrogates of terminally ill patients with cancer. Patients and Methods: This prospective, longitudinal, observational study included 377 family surrogates. Decisional regret was measured using the 5-item Decision Regret Scale, and 4 decisional regret trajectories were identified: resilient, delayed-recovery, late-emerging, and increasing-prolonged. Associations between bereavement outcomes (depressive symptoms, prolonged grief symptoms, and physical and mental health-related quality of life [HRQoL]) and decisional-regret trajectories were examined simultaneously by multivariate hierarchical linear modeling using the resilient trajectory as a reference. Results: Surrogates in the delayed-recovery, late-emerging, and increasing-prolonged trajectories experienced significantly higher symptoms of prolonged grief (β [95% CI], 1.815 [0.782 to 2.848]; 2.312 [0.834 to 3.790]; and 7.806 [2.681 to 12.931], respectively) and poorer physical HRQoL (−1.615 [−2.844 to −0.386]; −1.634 [−3.226 to −0.042]; and −4.749 [−9.380 to −0.118], respectively) compared with those in the resilient trajectory. Membership in the late-emerging and increasing-prolonged trajectories was associated with higher symptoms of depression (β [95% CI], 2.942 [1.045 to 4.839] and 8.766 [2.864 to 14.668], respectively), whereas only surrogates in the increasing-prolonged decisional-regret trajectory reported significantly worse mental HRQoL (−4.823 [−8.216 to −1.430]) than those in the resilient trajectory. Conclusions: Surrogates who experienced delayed-recovery, unresolved, or late-emerging decisional regret may carry ceaseless doubt, guilt, or self-blame for patient suffering, leading to profound symptoms of prolonged grief, depressive symptoms, and worse HRQoL over their first 2 bereavement years.
A Biomimic Nanobullet with Ameliorative Inflammatory Microenvironment for Alzheimer's Disease Treatments
Authors: Yanyue Wu, Jun Yang, Yiwan Geng, Xiyue Jiao, Zhiguo Lu, Tianlu Zhang, Ruichen Zhao, Jing Guo, Wenli Wang, Jing Wang, Xin Zhang
Journal: Advanced Healthcare Materials (2023)

Abstract Aβ oligomers, formed prior to diagnostic marker‐amyloid β (Aβ) plaques, can damage neurons and trigger neuroinflammation, which accelerate the neuronal injury in Alzheimer's disease (AD). Herein, the combination of eliminating the Aβ oligomers and alleviating the inflammation is a promising therapeutic strategy for AD. However, the presence of the blood‐brain barrier (BBB) and the intrinsic deficiencies of the drugs severely restrict their therapeutic effects. Inspired by the properties of rabies virus, a biomimic nanobullet (PBACR@NRs/SA) targeting neurons has been developed. The biomimic nanobullets possess the BBB penetrating character based on iron oxide nanorods; it can sequentially release rosmarinic acid and small interfering RNA targeting NF‐κB triggered by microenvironment, which improve the microenvironment inflammation and realize the cure for AD. Compared with non‐biomimic systems, the biomimic nanobullets exhibit a less caveolin‐dependent internalization pathway, which reduces ROS production and mitochondrial fission in neurons. Therefore, the biomimic nanobullet is hopeful for the treatment of ADs and provides a promising platform for other brain diseases’ treatments.
Association Between Pretreatment Chest Imaging and Immune Checkpoint Inhibitor Pneumonitis Among Patients With Lung Cancer
Authors: Alexander Wong, Maria Riley, Songzhu Zhao, Jessica Zimmer, Matthew Viveiros, Jing Gennie Wang, Vincent Esguerra, Mingjia Li, Gabrielle Lopez, Kari Kendra, David P. Carbone, Kai He, Asrar Alahmadi, Jacob Kaufman, Regan M. Memmott, Peter G. Shields, Jeremy Brownstein, Karl Haglund, Meng Welliver, Gregory A. Otterson, Carolyn J. Presley, Lai Wei, Dwight H. Owen, Kevin Ho
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Immune checkpoint inhibitors (ICIs) are a first-line and perioperative treatment for lung cancer. Pneumonitis is a potentially life-threatening complication of ICI treatment in 2% to 5% of patients; however, risk factors for developing ICI pneumonitis (ICI-p) remain undefined. Methods: We conducted a retrospective cohort study of consecutive patients with lung cancer who received at least one dose of ICI from 2015 through 2020 at The Ohio State University. Pneumonitis cases were documented by the treating oncologist and retrospectively evaluated for agreement between an oncologist and a pulmonologist. Patient demographic and clinical characteristics were recorded and summarized between those with and without pneumonitis for the overall cohort. Univariate and multivariable survival analyses using the Fine-Gray competing risk model were used to examine the associations. Results: A total of 471 patients with lung cancer were included, of which 402 had non–small cell lung cancer and 69 had small cell lung cancer; 39 (8%) patients in the overall cohort developed ICI-p. Preexisting interstitial abnormalities and prior chest radiation were both significantly associated with ICI-p on univariate analysis (hazard ratio [HR], 8.91; 95% CI, 4.69–16.92; P &lt;.001; and HR, 2.81; 95% CI, 1.50–5.28; P =.001). On multivariable analyses, interstitial abnormalities remained a strong independent risk factor for ICI-p when controlling for chest radiation and type of immunotherapy (HR, 9.77; 95% CI, 5.17–18.46; P &lt;.001). Among patients with ICI-p (n=39), those with severe (grade 3–5) pneumonitis had worse overall survival compared with those with mild (grade 1 or 2) pneumonitis ( P =.001). Abnormal pulmonary function test results at both 12 and 18 months prior to ICI initiation were not significantly associated with ICI-p. Conclusions: Preexisting interstitial abnormalities on chest CT and prior chest radiation are independent risk factors that are strongly associated with ICI-p in patients with lung cancer. These findings highlight a potential need for closer observation for ICI-p among patients with these risk factors.
Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221
Authors: Ciao-Sin Chen, Gary Zirpoli, William E. Barlow, G. Thomas Budd, Bryan McKiver, Lajos Pusztai, Gabriel N. Hortobagyi, Kathy S. Albain, M. Imad Damaj, Andrew K. Godwin, Alastair Thompson, N. Lynn Henry, Christine B. Ambrosone, Kathleen A. Stringer, Daniel L. Hertz
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Prior work suggests that patients with vitamin D insufficiency may have a higher risk of chemotherapy-induced peripheral neuropathy (CIPN) from paclitaxel. The objective of this study was to validate vitamin D insufficiency as a CIPN risk factor. Methods: We used data and samples from the prospective phase III SWOG S0221 (ClinicalTrials.gov identifier: NCT00070564 ) trial that compared paclitaxel-containing chemotherapy regimens for early-stage breast cancer. We quantified pretreatment 25-hydroxy-vitamin D in banked serum samples using a liquid chromatography-tandem mass spectrometry targeted assay. We tested the association between vitamin D insufficiency (≤20 ng/mL) and grade ≥3 sensory CIPN via multiple logistic regression and then adjusted for self-reported race, age, body mass index, and paclitaxel schedule (randomization to weekly or every-2-week dosing). We also tested the direct effect of vitamin D deficiency on mechanical hypersensitivity in mice randomized to a regular or vitamin D–deficient diet. Results: Of the 1,191 female patients in the analysis, 397 (33.3%) had pretreatment vitamin D insufficiency, and 195 (16.4%) developed grade ≥3 CIPN. Patients with vitamin D insufficiency had a higher incidence of grade ≥3 CIPN than those who had sufficient vitamin D (20.7% vs 14.2%; odds ratio [OR], 1.57; 95% CI, 1.14–2.15; P =.005). The association retained significance after adjusting for age and paclitaxel schedule (adjusted OR, 1.65; 95% CI, 1.18–2.30; P =.003) but not race (adjusted OR, 1.39; 95% CI, 0.98–1.97; P =.066). In the mouse experiments, the vitamin D–deficient diet caused mechanical hypersensitivity and sensitized mice to paclitaxel (both P &lt;.05). Conclusions: Pretreatment vitamin D insufficiency is the first validated potentially modifiable predictive biomarker of CIPN from paclitaxel. Prospective trials are needed to determine whether vitamin D supplementation prevents CIPN and improves treatment outcomes in patients with breast and other cancer types.
Impact of biological sex and sex hormones on molecular signatures of skeletal muscle at rest and in response to distinct exercise training modes
Authors: Mark W Pataky, Surendra Dasari, Kelly L Michie, Kyle J Sevits, A Aneesh Kumar, Katherine A Klaus, Carrie J Heppelmann, Matthew M Robinson, Rickey E Carter, Ian R Lanza, K Sreekumaran Nair
Journal: Cell Metabolism (2023)
Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice
Authors: Cara L. Green, Michaela E. Trautman, Krittisak Chaiyakul, Raghav Jain, Yasmine H. Alam, Reji Babygirija, Heidi H. Pak, Michelle M. Sonsalla, Mariah F. Calubag, Chung-Yang Yeh, Anneliese Bleicher, Grace Novak, Teresa T. Liu, Sarah Newman, Will A. Ricke, Kristina A. Matkowskyj, Irene M. Ong, Cholsoon Jang, Judith Simcox, Dudley W. Lamming
Journal: Cell Metabolism (2023)
Trilogy of drug repurposing for developing cancer and chemotherapy-induced heart failure co-therapy agent
Authors: Xin Chen, Xianggang Mu, Lele Ding, Xi Wang, Fei Mao, Jinlian Wei, Qian Liu, Yixiang Xu, Shuaishuai Ni, Lijun Jia, Jian Li
Journal: Acta Pharmaceutica Sinica B (2023)

Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.
Skeletal muscle-derived extracellular vesicles transport glycolytic enzymes to mediate muscle-to-bone crosstalk
Authors: Shixing Ma, Xiaotao Xing, Haisen Huang, Xin Gao, Xun Xu, Jian Yang, Chengcheng Liao, Xuanhao Zhang, Jinglun Liu, Weidong Tian, Li Liao
Journal: Cell Metabolism (2023)